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Abstract:

Vaccination remains the most important approach to offering protection from infectious
diseases. However, using needles and syringes for vaccine administration continues to be a
matter of concern, especially in developing countries. Re-use of needles, needle stick injuries
and improper disposal of needles in these regions of the world increase the risk of spreading
blood-borne pathogens among health care workers, patients and the wider community. The
concerns about the safe vaccination practice have led to an intensive effort to develop safe
delivery methods for vaccines and replace hypodermic injections. The opportunity to develop
a safe and effective method of vaccination using a minimally invasive method is becoming
real. The most promising approaches is microneedle (MN) array which has proven to be a
safe and cost effective method for vaccination. The current thesis was focus on dissolvable
MNs fabricated from 20%w/w poly(methyl vinyl ether/maleic acid) loaded with a model
antigen, ovalbumin (OVA). Various experiments were carried out during this thesis to
investigate the feasibility and efficacy of using MNs for vaccine delivery. The in vitro studies
showed that MNs loaded with OVA were strong enough to avoid breaking under high
compression force. The integrity of the primary and secondary structure of OVA loaded into
MN arrays successfully ensured. Further, MNs enhanced the release of OVA into the skin
compared to passive permeation. In in vivo studies, the OVA released from the MNs' matrix
upon insertion into mouse skin targeted dendrite cells (DCs). This thesis showed that av A
was engulfed by DCs, processed and migrated to the lymph nodes. Consequently, the
processed antigen encountered naive T cells, which led to initiation of robust humoral and
cellular immune responses indicated by production of IgG, IgG 1, IgG2a, IFN-γ and IL-4.
Interestingly, the PMVE/MA copolymer used to fabricate MNs seems to have adjuvant
effects, indicated by the higher IgG level of mice immunized using MNs fabricated from
PMVE/MA loaded with OVA compared with MNs fabricated from PMVE/MA and loaded
with OVA plus adjuvant imiquimod.